29 Aug 2024

First patient dosed in Guard Therapeutics’ phase 2b study POINTER

Guard Therapeutics today announced that the first patient has been dosed in the phase 2b clinical study POINTER with the drug candidate RMC-035 as a kidney-protective treatment in open-heart surgery.

"It is very gratifying that we have now been able to start the POINTER study as planned, it is an important milestone in our continued clinical development of RMC-035 in open-heart surgery. We start in Canada and intend to expand the study to several countries in Europe," said Guard Therapeutics CEO, Tobias Agervald.

The dosing of the first patient in the POINTER study took place at the Quebec Heart and Lung Institute (Institut Universitaire de Cardiologie et de Pneumologie De Quebec) under the supervision of Dr Maxime Laflamme. Patient recruitment in Europe (Germany, Spain and Czech Republic) is expected to begin in the fall.

The POINTER study is a randomized, double-blind, and placebo-controlled phase 2b study of RMC-035, and its primary objective is to establish an optimal dosing regimen and exact target population for treatment prior to a pivotal phase 3 study. The study is expected to include a total of approximately 160 patients distributed across two different dosage arms of RMC-035 (60 mg and 30 mg) and a control arm (placebo).

The primary efficacy measure of the study is the change in eGFR from the start of the study to the end of the follow-up period at 90 days after surgery. Patient recruitment is expected to last for approximately one year, and the overall study results are estimated to be available around 6 months later.

About the indication – kidney injury in open heart surgery

The company's drug candidate RMC-035 aims to counteract kidney injury that occurs in connection with open heart surgery and ultimately to reduce the risk of an irreversible loss of kidney function and future end-stage kidney disease that requires dialysis treatment or a kidney transplant.

Open heart surgery carried out using a heart-lung machine mainly includes coronary artery by-pass graft (CABG) with or without surgery of the heart valves or the aortic root. This type of surgery often causes significant damage to the kidneys. An important cause of a such damage is reduced blood flow to and oxygenation of the kidneys (ischemia-reperfusion injury). Hemolysis is another contributing cause, meaning that red blood cells are damaged, which in turn gives rise to kidney injury due to harmful breakdown products of the oxygen-carrying substance hemoglobin. Hemolysis occurs when blood is circulated outside the body, via the heart-lung machine, and following blood transfusions that are often given in connection with the procedure.
Additionally, as a result of lack of oxygen and hemolysis, a secondary inflammation often occurs which contributes to an ongoing injury process in the kidneys with the risk of scarring and permanent loss of kidney function.

About RMC-035

RMC-035 represents a completely new class of drugs (first-in-class) and consists of a recombinant and modified variant of the endogenous protein alpha-1-microglobulin. The investigational drug has the ability to protect cells and their mitochondria from damage caused by oxygen deprivation and elevated levels of the oxygen-binding and toxic protein heme. Favorable treatment effects of RMC-035 have been observed in several preclinical disease models. RMC-035 has a natural affinity for the kidneys and is primarily being developed as an intravenous kidney protective treatment for patients at high risk of developing acute kidney injury (AKI).

RMC-035 has obtained an Investigational New Drug (IND) clearance by the U.S. Food and Drug Administration (FDA) for the treatment of AKI in open-heart surgery. Additionally, RMC-035 has been granted Fast Track Designation by the FDA to reduce the risk of irreversible loss of kidney function, the need for dialysis treatment, or death after open-heart surgery in patients at elevated risk of AKI. Recent top-line results from the Phase 2 study AKITA demonstrated a statistically significant and clinically relevant favorable effect of RMC-035 on long-term kidney outcomes in this patient population. In addition to open-heart surgery, a second development program with RMC-035 was initiated with a recently completed Phase 1b clinical study in patients undergoing kidney transplantation.

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First patient dosed in Guard Therapeutics’ phase 2b study POINTER